ABSTRACT
The formation of either intramolecular or intermolecular covalent cross-links between amino acid residues in proteins is proving to be an extremely valuable tool in biochemistry with particular use in the study of protein-protein interactions. Naturally occurring inter and intramolecular cross-links are commonly found in proteins, the most common being the disulfide bond. Care must be taken in the size analysis of intramolecularly linked species in any denaturing medium since, unless the cross-linking reagent is cleaved by reduction, the intramolecularly cross-linked protein will not denature properly and will probably give falsely low molecular weight results. The early studies of Davies and Stark with dimethyl suberimidate showed that analysis of the reaction products reveals a set of species with molecular weights equal to integral multiples of the protomer molecular weight. The use of bifunctional maleimides is of considerable value in cross-linking between sulfhydryl groups.
